Eun-kyung Kim

Synthesis, characterization andIn vitro identification ofN 7-Guanine adduct of 2-bromopropane

Recently, we have reported that 2-bromopropane might have an immunotoxic potential in rats when exposed for 28 days. In the present studies, the possibility of 2í-deoxyguanosine adduct formation by 2-bromopropane was investigatedin vitro to elucidate molecular mechanism of 2-bromopropane-induced immunosuppression.N7-Guanine adduct of 2′-bromopropane (i.e.,N7-isopropyl guanine) was chemically synthesized and structurally characterized by analysis of UV,1H-NMR,13C-NMR, COSY and fast atom bombardment mass spectrometry to use as a reference material. Incubation of 2′-deoxyguanosine with an excess amount of 2-bromopropane in PBS buffer solution, pH 7.4, at 37°C for 16 h, followed by a thermal hydrolysis, produced a detectable amount ofN7-isopropyl guanine by an HPLC and UV analysis. The present results suggest that 2-bromopropane might form a DNA adduct inN7 position of 2′-deoxyguanosine at a physiological condition.

Design and synthesis of anticonvulsive agents as γ-vinyl GABA-based potential dual acting prodrugs and their biological activities

Abstract For the development of new anticonvulsive agents, γ-vinyl GABA (vigabatrin) and GABA mimetics derivatives were covalently coupled as potential dual acting prodrugs and evaluated for their anticonvulsive activities. Among the prepared compounds, 11 Download : Download high-res image (121KB) Download : Download full-size image Scheme 1 . showed the most potent anticonvulsive activity, a shorter onset time and a broader spectrum compared to vigabatrin.

Reactivity and suitability oft-boc-protected thiophosphotyrosine intermediate analogs for the solid or solution phase peptide synthesis

N-(tert-Butoxycarbonyl)-O-(dimethylthiophosphono)-L-tyrosine (6) andN-(tert-butoxycarbony)-O-(dicyanoethylthiophosphono)-L-tyrosine (15) were prepared as intermediates for the synthesis of thiophosphotyrosine-containing peptides. The reactivity and suitability of two compounds for the solid phase or solution phase peptide synthesis utilizingt-Boc chemistry were examined.

Identification of a N 7 -guanine adduct of 1-bromopropane in calf thymus DNA by mass spectrometry

As a replacement for chlorofluorocarbons that cause ozone depletion, 1-bromopropane has been widely used in work place. In the present study, the formation of N7-guanine adduct in DNA by 1-bromopropane was evaluated in vitro to elucidate the possible mechanism of its toxic action. N7-Propyl guanine was chemically synthesized and structurally characterized by NMR, UV, HPLC, and liquid chromatographyelectrospray ionization mass spectrometry (LC- ESI MS) for using as a reference standard. An incubation of 2ʹ-deoxyguanosine with 1-bromopropane produced N7-propyl adduct, which was identified by UV, HPLC and ESI-MS. In addition, N7-guanine adduct was also identified from the incorporation of calf thymus DNA with 1-bromopropane at the physiological condition by LC-ESI MS. Furthermore, the production of adduct was proportional to the amounts of 1-bromopropane used. These results indicated that the molecular mechanism underlying toxic effects of 1-bromopropane would be associated with the adduct formation on DNA at least in part.

Design, synthesis and anticonvulsive activities of potential prodrugs linked by two-carbon chain

For the development of new anticonvulsive agents, GABAmimetics such as nipecotic acid, isonipecotic acid, γ-aminobutyric acid (GABA), γ-vinyl GABA (vigabatrin) and valproic acid were covalently coupled through an ester bond by a two-carbon linker chain as potential prodrugs and evaluated for their anticonvulsive activities.